Diabetes mellitus is a clinical syndrome characterized by hyperglycemia due to insulin deficiency. It is by far the most common of the endocrine disorders and poses a serious challenge to health care worldwide. It is projected that by 2010, at least 239 million people will be affected by the disease (Thomas Mandrup-Poulsen, Clinical Review, Recent Advances, Diabetes, BMJ 316: 1221-25 (1998)). In Jamaica, the point prevalence of diabetes mellitus in the and over age group is estimated to be 17.9% (D. Ragoobirsingh et al., The Jamaican Diabetes Survey; A protocol for the Caribbean, Diabetes Care 18: 1277-79 (1995)), while in the United Kingdom, it is believed to be 2.4% of the adult population. In United States, diabetes ranks sixth as the primary cause of death, and has an estimated economic cost of between $85 billion and $92 billion, two thirds of which is a result of lost productivity because of hospitalizations or death (Jonathan C. Javitt and Yen-Pin Chiang, Economic Impact of Diabetes, in Diabetes in America, Ronald Aubert ed., pg. 601 (1995)). It is therefore clear that diabetes poses a threat to developing as well as developed countries.
Uncontrolled diabetes may result in the death of the patient or the development of complications of diabetes. Some of the characteristic long-term complications of diabetes are retinopathy with potential loss of vision, risk of developing atherosclerosis as well as peripheral vascular and cerebrovascular disease, nephropathy that may lead to renal failure, peripheral neuropathy with risk of developing foot ulcers and possible amputation.
Some of the most effective agents currently used to treat diabetes include synthetic substances such as sulfonylureas, biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors and lipase inhibitors. These agents have various side effects such as renal and hepatic impairment, hematological disturbances, cholestatic jaundice, lactic acidosis, anemia and headaches. There remains a need for anti-diabetic products that do not cause such side effects.
Oxidative stress is believed to be a major contributor to cardiovascular disease in individuals having diabetes mellitus (see Giugliano et al. (1995), “Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress?,” Metabolism 44:363-368). It is well documented that diabetes is associated with increased oxidative stress, as evidenced by the increased accumulation of lipid peroxides in the plasma of diabetic rats (Kakkar et al. (1995), “Lipid peroxidation and activity of antioxidant enzymes in diabetic rats,” Mol Cell Biochem, 151:113-119) and humans (Ozdemirler et al. (1995), “Peroxidation potential and antioxidant activity of serum in patients with diabetes mellitus and myocardial infarction,” Horm Metab Res 27:194-196). There remains a need for medicines that reduce oxidative stress and kidney damage in diabetic patients.
Familial hypercholesterolemia affects approximately 1 in 500 people worldwide, and the elevated serum cholesterol concentrations associated with it is responsible for more than 50% of the risk of fatal or non-fatal coronary heart disease by age 50 in men, and for at least 30% of the risk in women aged 60 and above. The prevalence of hypercholesterolemia in Jamaica is estimated at 31%. It is estimated that 37.13%, or 101 million people in the United States suffer from hypercholesterolemia.
The major conventional drugs used to treat hypercholesterolemia include the statins (Lovastatin, Pravastatin, Simvastatin, etc.) and Niacin (Nicotinic acid). Although these drugs are effective in lowering serum cholesterol levels, they result in several adverse effects. Statins, for example, result in gastrointestinal upset, muscle aches, and hepatitis. Rarer problems are myopathy (defined as muscle pain with serum creatine kinase concentrations of more than 1000 U per liter), rash, peripheral neuropathy, and insomnia. Niacin also results in adverse effects including flushing, abdominal pain, vomiting, headache, or elevated serum aminotransferase levels indicating liver damage. There remains a need for medicines that reduce total and LDL cholesterol levels in diabetic patients without such side effects.
Citation of any reference in section 3 of this application is not an admission that the reference is prior art.